Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

Harada, Junki; Miyata, Yasuyoshi; Araki, Kyohei; Matsuda, Tsuyoshi; Nagashima, Yoshiaki; Mukae, Yuta; Mistunari, Kensuke; Matsuo, Tomohiro; Ohba, Kenkichi; Mochizuki, Yoshinari; Sakai, Hideki

doi:10.21873/invivo.12429

Cited by 5 publications

(3 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TME components such as COMP play major roles in cancer progression and aggressiveness, making them an attractive target for cancer therapeutics [ 43 ]. Growing evidence has unveiled associations of COMP expression with a worse outcome in several solid cancer types, including breast, prostate, colorectal, bladder, and hepatocellular carcinoma [ 9 , 11 , 12 , 15 , 44 ]. For example, COMP levels in the serum of metastatic breast cancer patients were correlated with metastases to the liver, brain, and lung, as well as decreased OS, rendering it an independent prognostic biomarker [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Stromal cartilage oligomeric matrix protein as a tumorigenic driver in ovarian cancer via Notch3 signaling and epithelial-to-mesenchymal transition

Gorji-Bahri,

Krishna,

Hagerling

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background Cartilage oligomeric matrix protein (COMP), an extracellular matrix glycoprotein, is vital in preserving cartilage integrity. Further, its overexpression is associated with the aggressiveness of several types of solid cancers. This study investigated COMP’s role in ovarian cancer, exploring clinicopathological links and mechanistic insights. Methods To study the association of COMP expression in cancer cells and stroma with clinicopathological features of ovarian tumor patients, we analyzed an epithelial ovarian tumor cohort by immunohistochemical analysis. Subsequently, to study the functional mechanisms played by COMP, an in vivo xenograft mouse model and several molecular biology techniques such as transwell migration and invasion assay, tumorsphere formation assay, proximity ligation assay, and RT-qPCR array were performed. Results Based on immunohistochemical analysis of epithelial ovarian tumor tissues, COMP expression in the stroma, but not in cancer cells, was linked to worse overall survival (OS) of ovarian cancer patients. A xenograft mouse model showed that carcinoma-associated fibroblasts (CAFs) expressing COMP stimulate the growth and metastasis of ovarian tumors through the secretion of COMP. The expression of COMP was upregulated in CAFs stimulated with TGF-β. Functionally, secreted COMP by CAFs enhanced the migratory capacity of ovarian cancer cells. Mechanistically, COMP activated the Notch3 receptor by enhancing the Notch3-Jagged1 interaction. The dependency of the COMP effect on Notch was confirmed when the migration and tumorsphere formation of COMP-treated ovarian cancer cells were inhibited upon incubation with Notch inhibitors. Moreover, COMP treatment induced epithelial-to-mesenchymal transition and upregulation of active β-catenin in ovarian cancer cells. Conclusion This study suggests that COMP secretion by CAFs drives ovarian cancer progression through the induction of the Notch pathway and epithelial-to-mesenchymal transition.

show abstract

Section: Discussionmentioning

confidence: 99%

Stromal cartilage oligomeric matrix protein as a tumorigenic driver in ovarian cancer via Notch3 signaling and epithelial-to-mesenchymal transition

Gorji-Bahri,

Krishna,

Hagerling

et al. 2024

J Transl Med

View full text Add to dashboard Cite

show abstract

“…These expression levels are strongly associated with more aggressive pancreatobiliary-type (PB-type) exclusion of cytotoxic T-cells from the tumors and the presence of a denser collagen matrix [174]. Likewise, COMP is upregulated in bladder and colorectal cancers and is indicative of worse prognosis for the cancer patient [175,176].…”

Section: Glycoproteinsmentioning

confidence: 99%

“…Pro-tumorigenic in periampullary adenocarcinoma [174]; bladder cancer [175]; colorectal cancer [176].…”

Section: Cartilage Oligomeric Matrix Protein Compmentioning

confidence: 99%

Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators

Sorvina

Antoniou

Esmaeili

et al. 2023

Cancers

View full text Add to dashboard Cite

The extracellular matrix (ECM) is the complex three-dimensional network of fibrous proteins and proteoglycans that constitutes an essential part of every tissue to provide support for normal tissue homeostasis. Tissue specificity of the ECM in its topology and structure supports unique biochemical and mechanical properties of each organ. Cancers, like normal tissues, require the ECM to maintain multiple processes governing tumor development, progression and spread. A large body of experimental and clinical evidence has now accumulated to demonstrate essential roles of numerous ECM components in all cancer types. Latest findings also suggest that multiple tumor types express, and use to their advantage, atypical ECM components that are not found in the cancer tissue of origin. However, the understanding of cancer-specific expression patterns of these ECM proteins and their exact roles in selected tumor types is still sketchy. In this review, we summarize the latest data on the aberrant expression of bone and cartilage ECM proteins in epithelial cancers and their specific functions in the pathogenesis of carcinomas and discuss future directions in exploring the utility of this selective group of ECM components as future drug targets.

show abstract

Current look at the most promising proteomic and glycomic biomarkers of bladder cancer

Harsanyi,

Kianickova,

Katrlik

et al. 2024

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Background Bladder cancer (BC) belongs to the most frequent cancer types. The diagnostic process is still long and costly, with a high percentage of false-positive or -negative results. Due to the cost and lack of effectiveness, older methods need to be supplemented or replaced by a newer more reliable method. In this regard, proteins and glycoproteins pose high potential. Methods We performed an online search in PubMed/Medline, Scopus, and Web of Science databases to find relevant studies published in English up until May 2023. If applicable, we set the AUC threshold to 0.90 and sensitivity/specificity (SN/SP) to 90%. Findings Protein and glycoprotein biomarkers are a demonstrably viable option in BC diagnostics. Cholinesterase shows promise in progression-free survival. BLCA-4, ORM-1 along with HTRA1 in the detection of BC. Matrix metallopeptidase 9 exhibits potential for stratification of muscle-invasive subtypes with high negative predictive value for aggressive phenotypes. Distinguishing non-muscle invasive subtypes benefits from Keratin 17. Neu5Gc-modified UMOD glycoproteins pose potential in BC diagnosis, while fibronectin, laminin-5, collagen type IV, and lamprey immunity protein in early detection of BC.

show abstract

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

Cited by 5 publications

References 53 publications

Stromal cartilage oligomeric matrix protein as a tumorigenic driver in ovarian cancer via Notch3 signaling and epithelial-to-mesenchymal transition

Stromal cartilage oligomeric matrix protein as a tumorigenic driver in ovarian cancer via Notch3 signaling and epithelial-to-mesenchymal transition

Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators

Current look at the most promising proteomic and glycomic biomarkers of bladder cancer

Contact Info

Product

Resources

About